We investigated the role of excitatory amino acids in the activation of the phosphoinositide pathway during kainic acid-induced seizures in mature and immature animals. Kainic acid caused more severe seizures in the immature animals, but no hippocampal damage or induction of phosphoinositide hydrolysis. In mature animals, seizures were mild but severe hippocampal damage was seen and was associated with a marked and sustained release of inositol-trisphosphate, suggesting a role of this pathway and intracellular calcium stores in seizure-induced brain damage.